摘要：据8月10日刊《美国医学会杂志》上的一则对以往研究的回顾和分析报告披露，作为确定胎儿性别的一种无创伤性的方法，在妊娠7周后从母体血液中获得的无细胞胎儿DNA的检测效果良好，而基于尿液的检测则是不可靠的。
无创性产前胎儿性别确认可为人们提供一种重要的创伤性的细胞遗传学性别确认的替代检测，后者目前是确认胎儿性别和单基因病的最可靠的标准。根据文章的背景资料，羊膜穿刺术会带来数量少但却是可检测得到的与手术有关的流产发生率；超声波检查可最早在妊娠11周时（尽管并不可靠）确定胎儿的性别。文章的作者写道：“能够有可靠的无创性确认胎儿性别的替代方法将可减少无意识的胎儿流产，它估计会受到怀有携带疾病风险的胎儿的孕妇的欢迎。”
用无细胞胎儿DNA作为产前确认胎儿性别的无创性检测方法为人们提供了一种对某些遗传性疾病进行创伤性检查的替代方法。在某些国家中（如荷兰、英国、法国和西班牙），这种检测已经过渡成为常规的临床检查（尽管缺乏对这种测试的正式评估）。根据文章的背景资料：“最近，有公司开始在互联网上直接向消费者提供这种技术。这些检测是以非医疗用途来营销的，其营销对象是那些好奇的即将成为父母的人。这些检测承诺，其精确性在某些情况下可高达95%至99%，而检测适用的时间可早至妊娠的第5-7周。”
马里兰州贝塞斯达国立卫生学院的Stephanie A. Devaney, Ph.D.及其同事对以往的研究进行了系统的回顾和荟萃分析以检查无细胞胎儿DNA检测分析的有效性；该检查所描述的是在母体样本中探测到Y染色体序列的能力，以及该测试在临床上的有效性（表现为正确识别胎儿性别的能力）。研究人员挑了57则研究（其中包括了80个数据组[它代表了3524例怀有男婴的妊娠和3017例怀有女婴的妊娠]）并对其进行了分析。
研究人员发现，该测试的总体敏感性为95.4%、特异性为98.6%、阳性预测值为98.8%、阴性预测值为94.8%。用母体血液进行检测的精度很高。所用的DNA方法学和所处的妊娠期对检测精度有着最大的影响，实时定量多聚酶链反应(RTQ-PCR)的检测精度超过常规的PCR。如果用RTQ-PCR对某个在怀孕期间采集的血样本（如果那时血液中存在有足够的无细胞胎儿DNA时，即妊娠7周或更久的时候）进行测试的话，其测试性能会很好；测试性能最好的时候是在妊娠20周之后。在妊娠7周之前用血液进行测试，而所有其它的用尿液进行测试的做法被发现是不可靠的。
文章的作者写道：“在妊娠期较晚时的测试性能的提高可能与随着胎儿和胎盘的发育母体血液中无细胞胎儿DNA浓度的增加有关。这可以解释为什么在妊娠7周之前测试性能不佳以及在妊娠晚期则有着近乎完美的测试性能。”
研究人员提示，这一“技术可用于在早期胎儿中发现需要做追踪测试的与性别有关的疾病风险的临床情况中。”
生物探索推荐英文论文摘要：
Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA
ABSTRACT
Context Noninvasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. In some countries this testing has transitioned to clinical care, despite the absence of a formal assessment of performance.
Objective To document overall test performance of noninvasive fetal sex determination using cell-free fetal DNA and to identify variables that affect performance.
Data Sources Systematic review and meta-analysis with search of PubMed (January 1, 1997-April 17, 2011) to identify English-language human studies reporting primary data. References from review articles were also searched.
Study Selection and Data Extraction Abstracts were read independently to identify studies reporting primary data suitable for analysis. Covariates included publication year, sample type, DNA amplification methodology, Y chromosome sequence, and gestational age. Data were independently extracted by 2 reviewers.
Results From 57 selected studies, 80 data sets (representing 3524 male-bearing pregnancies and 3017 female-bearing pregnancies) were analyzed. Overall performance of the test to detect Y chromosome sequences had the following characteristics: sensitivity, 95.4% (95% confidence interval [CI], 94.7%-96.1%) and specificity, 98.6% (95% CI, 98.1%-99.0%); diagnostic odds ratio (OR), 885; positive predictive value, 98.8%; negative predictive value, 94.8%; area under curve (AUC), 0.993 (95% CI, 0.989-0.995), with significant interstudy heterogeneity. DNA methodology and gestational age had the largest effects on test performance. Methodology test characteristics were AUC, 0.988 (95% CI, 0.979-0.993) for polymerase chain reaction (PCR) and AUC, 0.996 (95% CI, 0.993-0.998) for real-time quantitative PCR (RTQ-PCR) (P = .02). Gestational age test characteristics were AUC, 0.989 (95% CI, 0.965-0.998) (<7 weeks); AUC, 0.994 (95% CI, 0.987-0.997) (7-12 weeks); AUC, 0.992 (95% CI, 0.983-0.996) (13-20 weeks); and AUC, 0.998 (95% CI, 0.990-0.999) (>20 weeks) (P = .02 for comparison of diagnostic ORs across age ranges). RTQ-PCR (sensitivity, 96.0%; specificity, 99.0%) outperformed conventional PCR (sensitivity, 94.0%; specificity, 97.3%). Testing after 20 weeks (sensitivity, 99.0%; specificity, 99.6%) outperformed testing prior to 7 weeks (sensitivity, 74.5%; specificity, 99.1%), testing at 7 through 12 weeks (sensitivity, 94.8%; specificity, 98.9%), and 13 through 20 weeks (sensitivity, 95.5%; specificity, 99.1%).
Conclusions Despite interstudy variability, performance was high using maternal blood. Sensitivity and specificity for detection of Y chromosome sequences was greatest using RTQ-PCR after 20 weeks' gestation. Tests using urine and tests performed before 7 weeks' gestation were unreliable.
KEYWORDS: chromosomes, human, y, genetic diseases, y-linked, genetic techniques, prenatal diagnosis, reverse transcriptase polymerase chain reaction, sex determination (genetics).
生物探索推荐英文原文报道：
Tests That Use DNA from Mother’s Blood to Determine Sex of Fetus Often Effective
As a noninvasive method of determining the sex of a fetus, tests using cell-free fetal DNA obtained from the mother's blood after 7 weeks gestation performed well, while urine-based tests appear to be unreliable, according to a review and analysis of previous studies, reported in the August 10 issue of JAMA.
Noninvasive prenatal determination of fetal sex could provide an important alternative to invasive cytogenetic determination, which is currently the gold standard for determining sex and single-gene disorders. Amniocentesis has small but measurable rates of procedure-related pregnancy loss; and sonography can be performed as early as 11 weeks' gestation to determine fetal sex, although not reliably, according to background information in the article. "The availability of a reliable noninvasive alternative to determine fetal sex would reduce unintended fetal losses and would presumably be welcomed by pregnant women carrying fetuses at risk for disorders," the authors write.
Using cell-free fetal DNA as a noninvasive method for prenatal determination of fetal sex provides an alternative to invasive techniques for some heritable disorders. In some countries, such as the Netherlands, the United Kingdom, France, and Spain, this testing has already transitioned to routine clinical care despite the absence of a formal assessment of its performance. "More recently, companies have begun offering this technology directly to the consumer over the Internet. The tests are marketed for nonmedical use to curious parents-to-be with promises in some cases of accuracy as high as 95 percent to 99 percent at as early as 5 to 7 weeks' gestation," according to background information in the article.
Stephanie A. Devaney, Ph.D., of the National Institutes of Health, Bethesda, Md., and colleagues performed a systematic review and meta-analysis of previous research to examine the analytic validity of cell-free fetal DNA testing, which describes the test's ability to detect Y chromosome sequences within maternal samples, as well as the clinical validity of the test, as indicated by its ability to correctly identify fetal sex. The researchers selected 57 studies (which included 80 data sets [representing 3,524 male-bearing pregnancies and 3,017 female-bearing pregnancies]) for inclusion in the analysis.
The researchers found that the overall performance of the tests had sensitivity of 95.4 percent, specificity of 98.6 percent, positive predictive value, 98.8 percent, and negative predictive value, 94.8 percent. Performance was high using maternal blood. DNA methodology and gestational age had the largest effects on test performance, with real-time quantitative polymerase chain reaction (RTQ-PCR) outperforming conventional PCR. Test performance was high if performed using RTQ-PCR on a blood sample taken at a time during pregnancy when sufficient cell-free fetal DNA was present (7 weeks' gestation or later), with the best performance after 20 weeks' gestation. Testing performed prior to 7 weeks' gestation using blood, and all tests using urine, were found unreliable.
"The improved performance with later gestation is likely attributable to the increased concentration of cell-free fetal DNA within maternal blood as the fetus and placenta develop. This would explain the poor performance of the test prior to 7 weeks' gestation and the near-perfect performance in the third trimester," the authors write.
The researchers suggest that this "technology can be useful in clinical settings for early detection of fetuses at risk for sex-linked disorders requiring follow-up testing."
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